Display options
Share it on

Sci Rep. 2016 Sep 26;6:33798. doi: 10.1038/srep33798.

Polyoxazoline multivalently conjugated with indocyanine green for sensitive in vivo photoacoustic imaging of tumors.

Scientific reports

Kengo Kanazaki, Kohei Sano, Akira Makino, Tsutomu Homma, Masahiro Ono, Hideo Saji

Affiliations

  1. Department of Patho-Functional Bioanalysis Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto, 606-8501, Japan.
  2. Medical Imaging Project, Corporate R&D Headquarters, Canon Inc., 3-30-2 Shimomaruko, Ohta-ku, Tokyo, 146-8501, Japan.
  3. Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
  4. Biomedical Imaging Research Center, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui, 910-1193, Japan.

PMID: 27667374 PMCID: PMC5036052 DOI: 10.1038/srep33798

Abstract

Photoacoustic imaging, which enables high-resolution imaging in deep tissues, has lately attracted considerable attention. For tumor imaging, photoacoustic probes have been proposed to enhance the photoacoustic effect to improve detection sensitivity. Here, we evaluated the feasibility of using a biocompatible hydrophilic polymer, polyoxazoline, conjugated with indocyanine green (ICG) as a tumor-targeted photoacoustic probe via enhanced permeability and retention effect. ICG molecules were multivalently conjugated to partially hydrolyzed polyoxazoline, thereby serving as highly sensitive photoacoustic probes. Interestingly, loading multiple ICG molecules to polyoxazoline significantly enhanced photoacoustic signal intensity under the same ICG concentration. In vivo biodistribution studies using tumor bearing mice demonstrated that 5% hydrolyzed polyoxazoline (50 kDa) conjugated with ICG (ICG/polyoxazoline = 7.8), P14-ICG7.8, showed relatively high tumor accumulation (9.4%ID/g), resulting in delivery of the highest dose of ICG among the probes tested. P14-ICG7.8 enabled clear visualization of the tumor regions by photoacoustic imaging 24 h after administration; the photoacoustic signal increased in proportion with the injected dose. In addition, the signal intensity in blood vessels in the photoacoustic images did not show much change, which was attributed to the high tumor-to-blood ratios of P14-ICG7.8. These results suggest that polyoxazoline-ICG would serve as a robust probe for sensitive photoacoustic tumor imaging.

References

  1. Bioconjug Chem. 2011 May 18;22(5):976-86 - PubMed
  2. Biomacromolecules. 2011 Oct 10;12(10):3797-804 - PubMed
  3. Biochem Biophys Res Commun. 2015 Aug 28;464(3):820-5 - PubMed
  4. Nature. 2008 Apr 3;452(7187):580-9 - PubMed
  5. Nanomedicine. 2015 Nov;11(8):2051-60 - PubMed
  6. J Control Release. 2016 Mar 28;226:115-23 - PubMed
  7. J Comb Chem. 2005 Jan-Feb;7(1):10-3 - PubMed
  8. J Biomed Opt. 2015 Sep;20(9):096006 - PubMed
  9. Bioorg Med Chem Lett. 2011 Jan 1;21(1):280-4 - PubMed
  10. ACS Nano. 2015 Mar 24;9(3):2711-9 - PubMed
  11. Mol Pharm. 2013 Jan 7;10 (1):360-77 - PubMed
  12. Biomaterials. 2011 May;32(13):3435-46 - PubMed
  13. Macromol Rapid Commun. 2012 Oct 15;33(19):1613-31 - PubMed
  14. Bioconjug Chem. 2003 May-Jun;14(3):581-7 - PubMed
  15. J Control Release. 2008 Jan 22;125(2):87-95 - PubMed
  16. Science. 2012 Mar 23;335(6075):1458-62 - PubMed
  17. Bioconjug Chem. 2010 May 19;21(5):797-802 - PubMed
  18. Adv Drug Deliv Rev. 2011 Mar 18;63(3):129-30 - PubMed
  19. J Am Chem Soc. 2006 Mar 22;128(11):3784-8 - PubMed
  20. J Biomed Opt. 2014 Sep;19(9):96002 - PubMed
  21. Microvasc Res. 1998 Mar;55(2):146-52 - PubMed
  22. J Am Chem Soc. 2013 Jul 31;135(30):11015-22 - PubMed
  23. J Control Release. 2014 Sep 10;189:90-104 - PubMed
  24. Br J Cancer. 2000 May;82(9):1513-8 - PubMed
  25. Small. 2015 Jun 10;11(22):2675-86 - PubMed
  26. ACS Nano. 2012 Jun 26;6(6):4694-701 - PubMed
  27. J Biomed Opt. 2014 Sep;19(9):090501 - PubMed
  28. J Clin Invest. 1960 Apr;39:592-600 - PubMed
  29. J Biomater Sci Polym Ed. 2010;21(2):225-36 - PubMed
  30. Nat Methods. 2010 Aug;7(8):603-14 - PubMed
  31. J Control Release. 2007 Jun 22;119(3):291-300 - PubMed
  32. ACS Nano. 2015 Oct 27;9(10 ):9517-27 - PubMed

Publication Types